NIPBL

Protein identityUniProt · HPA

UniProt accession

Q6KC79

Gene

NIPBL

Ensembl

ENSG00000164190

Chromosome

5

Canonical length

2804 aa

Protein class

Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Vesicles,Cytosol

OverviewNCBI Gene

This gene encodes the homolog of the Drosophila melanogaster Nipped-B gene product and fungal Scc2-type sister chromatid cohesion proteins. The Drosophila protein facilitates enhancer-promoter communication of remote enhancers and plays a role in developmental regulation. It is also homologous to a family of chromosomal adherins with broad roles in sister chromatid cohesion, chromosome condensation, and DNA repair. The human protein has a bipartite nuclear targeting sequence and a putative HEAT repeat. Condensins, cohesins and other complexes with chromosome-related functions also contain HEAT repeats. Mutations in this gene result in Cornelia de Lange syndrome, a disorder characterized by dysmorphic facial features, growth delay, limb reduction defects, and cognitive disability. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

2804 residues, UniProt reviewed canonical sequence.

>Q6KC79|NIPBL
     1  MNGDMPHVPI TTLAGIASLT DLLNQLPLPS PLPATTTKSL LFNARIAEEV NCLLACRDDN
    61  LVSQLVHSLN QVSTDHIELK DNLGSDDPEG DIPVLLQAVL ARSPNVFREK SMQNRYVQSG
   121  MMMSQYKLSQ NSMHSSPASS NYQQTTISHS PSSRFVPPQT SSGNRFMPQQ NSPVPSPYAP
   181  QSPAGYMPYS HPSSYTTHPQ MQQASVSSPI VAGGLRNIHD NKVSGPLSGN SANHHADNPR
   241  HGSSEDYLHM VHRLSSDDGD SSTMRNAASF PLRSPQPVCS PAGSEGTPKG SRPPLILQSQ
   301  SLPCSSPRDV PPDILLDSPE RKQKKQKKMK LGKDEKEQSE KAAMYDIISS PSKDSTKLTL
   361  RLSRVRSSDM DQQEDMISGV ENSNVSENDI PFNVQYPGQT SKTPITPQDI NRPLNAAQCL
   421  SQQEQTAFLP ANQVPVLQQN TSVAAKQPQT SVVQNQQQIS QQGPIYDEVE LDALAEIERI
   481  ERESAIERER FSKEVQDKDK PLKKRKQDSY PQEAGGATGG NRPASQETGS TGNGSRPALM
   541  VSIDLHQAGR VDSQASITQD SDSIKKPEEI KQCNDAPVSV LQEDIVGSLK STPENHPETP
   601  KKKSDPELSK SEMKQSESRL AESKPNENRL VETKSSENKL ETKVETQTEE LKQNESRTTE
   661  CKQNESTIVE PKQNENRLSD TKPNDNKQNN GRSETTKSRP ETPKQKGESR PETPKQKSDG
   721  HPETPKQKGD GRPETPKQKG ESRPETPKQK NEGRPETPKH RHDNRRDSGK PSTEKKPEVS
   781  KHKQDTKSDS PRLKSERAEA LKQRPDGRSV SESLRRDHDN KQKSDDRGES ERHRGDQSRV
   841  RRPETLRSSS RNEHGIKSDS SKTDKLERKH RHESGDSRER PSSGEQKSRP DSPRVKQGDS
   901  NKSRSDKLGF KSPTSKDDKR TEGNKSKVDT NKAHPDNKAE FPSYLLGGRS GALKNFVIPK
   961  IKRDKDGNVT QETKKMEMKG EPKDKVEKIG LVEDLNKGAK PVVVLQKLSL DDVQKLIKDR
  1021  EDKSRSSLKP IKNKPSKSNK GSIDQSVLKE LPPELLAEIE STMPLCERVK MNKRKRSTVN
  1081  EKPKYAEISS DEDNDSDEAF ESSRKRHKKD DDKAWEYEER DRRSSGDHRR SGHSHEGRRS
  1141  SGGGRYRNRS PSDSDMEDYS PPPSLSEVAR KMKKKEKQKK RKAYEPKLTP EEMMDSSTFK
  1201  RFTASIENIL DNLEDMDFTA FGDDDEIPQE LLLGKHQLNE LGSESAKIKA MGIMDKLSTD
  1261  KTVKVLNILE KNIQDGSKLS TLLNHNNDTE EEERLWRDLI MERVTKSADA CLTTINIMTS
  1321  PNMPKAVYIE DVIERVIQYT KFHLQNTLYP QYDPVYRLDP HGGGLLSSKA KRAKCSTHKQ
  1381  RVIVMLYNKV CDIVSSLSEL LEIQLLTDTT ILQVSSMGIT PFFVENVSEL QLCAIKLVTA
  1441  VFSRYEKHRQ LILEEIFTSL ARLPTSKRSL RNFRLNSSDM DGEPMYIQMV TALVLQLIQC
  1501  VVHLPSSEKD SNAEEDSNKK IDQDVVITNS YETAMRTAQN FLSIFLKKCG SKQGEEDYRP
  1561  LFENFVQDLL STVNKPEWPA AELLLSLLGR LLVHQFSNKS TEMALRVASL DYLGTVAARL
  1621  RKDAVTSKMD QGSIERILKQ VSGGEDEIQQ LQKALLDYLD ENTETDPSLV FSRKFYIAQW
  1681  FRDTTLETEK AMKSQKDEES SEGTHHAKEI ETTGQIMHRA ENRKKFLRSI IKTTPSQFST
  1741  LKMNSDTVDY DDACLIVRYL ASMRPFAQSF DIYLTQILRV LGENAIAVRT KAMKCLSEVV
  1801  AVDPSILARL DMQRGVHGRL MDNSTSVREA AVELLGRFVL CRPQLAEQYY DMLIERILDT
  1861  GISVRKRVIK ILRDICIEQP TFPKITEMCV KMIRRVNDEE GIKKLVNETF QKLWFTPTPH
  1921  NDKEAMTRKI LNITDVVAAC RDTGYDWFEQ LLQNLLKSEE DSSYKPVKKA CTQLVDNLVE
  1981  HILKYEESLA DSDNKGVNSG RLVACITTLF LFSKIRPQLM VKHAMTMQPY LTTKCSTQND
  2041  FMVICNVAKI LELVVPLMEH PSETFLATIE EDLMKLIIKY GMTVVQHCVS CLGAVVNKVT
  2101  QNFKFVWACF NRYYGAISKL KSQHQEDPNN TSLLTNKPAL LRSLFTVGAL CRHFDFDLED
  2161  FKGNSKVNIK DKVLELLMYF TKHSDEEVQT KAIIGLGFAF IQHPSLMFEQ EVKNLYNNIL
  2221  SDKNSSVNLK IQVLKNLQTY LQEEDTRMQQ ADRDWKKVAK QEDLKEMGDV SSGMSSSIMQ
  2281  LYLKQVLEAF FHTQSSVRHF ALNVIALTLN QGLIHPVQCV PYLIAMGTDP EPAMRNKADQ
  2341  QLVEIDKKYA GFIHMKAVAG MKMSYQVQQA INTCLKDPVR GFRQDESSSA LCSHLYSMIR
  2401  GNRQHRRAFL ISLLNLFDDT AKTDVTMLLY IADNLACFPY QTQEEPLFIM HHIDITLSVS
  2461  GSNLLQSFKE SMVKDKRKER KSSPSKENES SDSEEEVSRP RKSRKRVDSD SDSDSEDDIN
  2521  SVMKCLPENS APLIEFANVS QGILLLLMLK QHLKNLCGFS DSKIQKYSPS ESAKVYDKAI
  2581  NRKTGVHFHP KQTLDFLRSD MANSKITEEV KRSIVKQYLD FKLLMEHLDP DEEEEEGEVS
  2641  ASTNARNKAI TSLLGGGSPK NNTAAETEDD ESDGEDRGGG TSGSLRRSKR NSDSTELAAQ
  2701  MNESVDVMDV IAICCPKYKD RPQIARVVQK TSSGFSVQWM AGSYSGSWTE AKRRDGRKLV
  2761  PWVDTIKESD IIYKKIALTS ANKLTNKVVQ TLRSLYAAKD GTSS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NIPBL can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0

Highest tissue expression

28 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about NIPBL.

Disease | AllUniProt

Conditions NIPBL is implicated in, by any mechanism.

• Cornelia de Lange syndrome 1 (CDLS1) MIM:122470

Disease | GeneticClinVar

592 pathogenic / likely-pathogenic of 2,388 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Cornelia de Lange syndrome 1
• NIPBL-related disorder
• Inborn genetic diseases
• De Lange syndrome
• Intellectual disability

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.03

gnomAD pLI

1

gnomAD missense Z

5.57

DepMap mean gene effect

-0.57

DepMap dependency class

common

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 11% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• brain development
• cellular response to X-ray
• chromatin looping
• chromatin remodeling
• cognition
• developmental growth
• digestive tract development
• DNA damage response
• ear morphogenesis
• embryonic digestive tract morphogenesis
• embryonic forelimb morphogenesis
• embryonic viscerocranium morphogenesis
• establishment of mitotic sister chromatid cohesion
• establishment of protein localization to chromatin
• eye morphogenesis
• face morphogenesis
• fat cell differentiation
• forelimb morphogenesis
• gallbladder development
• heart morphogenesis
• intracellular protein localization
• maintenance of mitotic sister chromatid cohesion
• metanephros development
• mitotic sister chromatid cohesion
• mitotic sister chromatid segregation
• negative regulation of transcription by RNA polymerase II
• outflow tract morphogenesis
• positive regulation of multicellular organism growth
• positive regulation of neuron migration
• positive regulation of ossification
• positive regulation of transcription by RNA polymerase II
• regulation of developmental growth
• regulation of embryonic development
• regulation of hair cycle
• replication-born double-strand break repair via sister chromatid exchange
• sensory perception of sound
• somatic stem cell population maintenance
• uterus morphogenesis
• external genitalia morphogenesis

Molecular functions

• chromatin binding
• chromo shadow domain binding
• cohesin loader activity
• histone deacetylase binding
• mediator complex binding
• promoter-specific chromatin binding
• transcription corepressor activity

Cellular components

• chromatin
• cytosol
• extracellular exosome
• integrator complex
• nucleoplasm
• nucleus
• Scc2-Scc4 cohesin loading complex
• SMC loading complex

Protein domainsUniProt · Pfam · InterPro

• Armadillo-like helical
• Armadillo-type fold
• Sister chromatid cohesion C-terminal domain
• HEAT repeat associated with sister chromatid cohesion protein
• Scc2/Nipped-B family
• HEAT repeat associated with sister chromatid cohesion
• Sister chromatid cohesion C-terminus

KeywordsUniProt

• Acetylation
• Activator
• Cell cycle
• Chromosome
• Developmental protein
• Intellectual disability
• Nucleus
• Phosphoprotein
• Repeat
• Transcription
• Transcription regulation

InteractionsUniProt · HPA

Protein binding partners of NIPBL in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• BRD4
• PRR12
• RAD21
• ZNF609
• CBX3
• AR
• CBX5
• MAU2
• SMC1A
• STAG2